Prostate cancer is the most common form of non-skin malignancy and a leading cause of cancer-related death in men in the United States. Prostate cancer generally targets men over age 50, usually with few or no symptoms of its early stages. Treatment options for prostate cancer, especially for hormone refractory prostate cancer, can be very limited.
Early detection can be important for effective treatment and management of prostate cancer. For two decades serum prostate specific antigen (“PSA”) has been used as a marker for prostate cancer detection. The advent of PSA as a biomarker has enabled early detection of prostate cancer and hence improved clinical outcome, and prostate cancer can often be found early by testing the amount of PSA in the blood. However, a low PSA level is not a guarantee of disease-free status, and an elevated PSA level is frequently associated with a negative biopsy. Moreover, elevated serum PSA lacks the specificity required to distinguish prostate cancer from other prostatic disorders, such as benign prostatic hyperplasia (“BPH”) and prostatitis (1, 2). Furthermore, PSA lacks the sensitivity to detect a large fraction of early stage tumors, since more than 15% of men with a normal serum PSA level have biopsy-proven prostate cancer (3). In addition, histological confirmation of prostate cancer requires multiple biopsies of the prostate using procedures that are too invasive to repeat at regular intervals. Finally, autopsy data from American men indicates that there is about a 49% lifetime risk of developing prostate cancer. However, the risk of having clinically detected prostate cancer in the same population is less than 18% (28), suggesting that the development and progression of prostate cancer is different in different men. Prostate cancer is a heterogeneous disease (29) whose development and progression involve changes in expression of a number of genes that determine oncogenic transformation, survival, and invasiveness of prostate cancer cells. In this context, reliable detection and prediction of outcome of the disease may benefit from identification of changes in expression of genes that influence disease development and progression.
Thus, an unmet need remains for non-invasive methods to detect markers of prostate cancer with specificity and sensitivity in biological samples, including without limitation, tissues and bodily fluids such as urine or blood.